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Kynurenine/tryptophan ratio for detection of active tuberculosis in adults with HIV prior to antiretroviral therapy

Olsson, Oskar LU orcid ; Skogmar, Sten LU ; Tesfaye, Fregenet LU ; Mulleta, Daba ; Jansson, Marianne LU and Björkman, Per LU orcid (2022) In AIDS 36(9). p.1245-1253
Abstract

Objective: The aim of this study was to assess the performance of kynurenine/tryptophan ratio for tuberculosis (TB) case-finding among antiretroviral therapy (ART)-naive people with HIV (PWH), and to investigate other factors associated with kynurenine/tryptophan ratio in this population. Design: A nested case-control study based on a cohort of 812 ambulatory PWH in the Oromia region, Ethiopia. Methods: At enrolment, all participants submitted sputum samples for bacteriological TB investigations. Concentrations of kynurenine and tryptophan in plasma were quantified using liquid chromatography-mass spectrometry. Receiver operator characteristic curves were constructed to assess diagnostic performance (area under the curve; AUC) for... (More)

Objective: The aim of this study was to assess the performance of kynurenine/tryptophan ratio for tuberculosis (TB) case-finding among antiretroviral therapy (ART)-naive people with HIV (PWH), and to investigate other factors associated with kynurenine/tryptophan ratio in this population. Design: A nested case-control study based on a cohort of 812 ambulatory PWH in the Oromia region, Ethiopia. Methods: At enrolment, all participants submitted sputum samples for bacteriological TB investigations. Concentrations of kynurenine and tryptophan in plasma were quantified using liquid chromatography-mass spectrometry. Receiver operator characteristic curves were constructed to assess diagnostic performance (area under the curve; AUC) for kynurenine, tryptophan, and kynurenine/tryptophan ratio. Sensitivity, specificity, and predictive values were calculated. Kynurenine/tryptophan ratios were correlated to plasma levels of nine inflammation mediators, plasma HIV RNA levels, CD4+cell count, BMI, and mid-upper arm circumference (MUAC). Results: We included 124 individuals with HIV-TB coinfection (HIV+/TB+) and 125 with HIV mono-infection (HIV+/TB-). Tryptophan levels were lower in HIV+/TB+ than in HIV+/TB-(median 19.5 vs. 29.8 μmol/l, P < 0.01), while kynurenine levels were similar between these groups (median 2.95 vs. 2.94 μmol/l, P = 0.62). Median kynurenine/tryptophan ratio was 0.15 in HIV+/TB+, significantly higher compared with HIV+/TB-(0.11; P < 0.01), with AUC 0.70 for TB detection. Kynurenine/tryptophan ratio was positively correlated to plasma HIV RNA levels, IP-10, IL-18, and IL-27, and negatively correlated to CD4+cell count, BMI, and MUAC (all P < 0.01). Conclusion: Among ART-naive PWH, kynurenine/tryptophan ratio has modest potential for TB discrimination, limiting its utility for TB case-finding in this population.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biomarkers, HIV, kynurenine, tryptophan, tuberculosis
in
AIDS
volume
36
issue
9
pages
9 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:35703207
  • scopus:85134429527
ISSN
0269-9370
DOI
10.1097/QAD.0000000000003235
language
English
LU publication?
yes
id
1dc4cdbd-d153-4385-b001-e6ebbff047f7
date added to LUP
2022-09-15 14:57:56
date last changed
2024-06-09 21:42:43
@article{1dc4cdbd-d153-4385-b001-e6ebbff047f7,
  abstract     = {{<p>Objective: The aim of this study was to assess the performance of kynurenine/tryptophan ratio for tuberculosis (TB) case-finding among antiretroviral therapy (ART)-naive people with HIV (PWH), and to investigate other factors associated with kynurenine/tryptophan ratio in this population. Design: A nested case-control study based on a cohort of 812 ambulatory PWH in the Oromia region, Ethiopia. Methods: At enrolment, all participants submitted sputum samples for bacteriological TB investigations. Concentrations of kynurenine and tryptophan in plasma were quantified using liquid chromatography-mass spectrometry. Receiver operator characteristic curves were constructed to assess diagnostic performance (area under the curve; AUC) for kynurenine, tryptophan, and kynurenine/tryptophan ratio. Sensitivity, specificity, and predictive values were calculated. Kynurenine/tryptophan ratios were correlated to plasma levels of nine inflammation mediators, plasma HIV RNA levels, CD4<sub>+</sub>cell count, BMI, and mid-upper arm circumference (MUAC). Results: We included 124 individuals with HIV-TB coinfection (HIV+/TB+) and 125 with HIV mono-infection (HIV+/TB-). Tryptophan levels were lower in HIV+/TB+ than in HIV+/TB-(median 19.5 vs. 29.8 μmol/l, P &lt; 0.01), while kynurenine levels were similar between these groups (median 2.95 vs. 2.94 μmol/l, P = 0.62). Median kynurenine/tryptophan ratio was 0.15 in HIV+/TB+, significantly higher compared with HIV+/TB-(0.11; P &lt; 0.01), with AUC 0.70 for TB detection. Kynurenine/tryptophan ratio was positively correlated to plasma HIV RNA levels, IP-10, IL-18, and IL-27, and negatively correlated to CD4<sub>+</sub>cell count, BMI, and MUAC (all P &lt; 0.01). Conclusion: Among ART-naive PWH, kynurenine/tryptophan ratio has modest potential for TB discrimination, limiting its utility for TB case-finding in this population.</p>}},
  author       = {{Olsson, Oskar and Skogmar, Sten and Tesfaye, Fregenet and Mulleta, Daba and Jansson, Marianne and Björkman, Per}},
  issn         = {{0269-9370}},
  keywords     = {{biomarkers; HIV; kynurenine; tryptophan; tuberculosis}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{9}},
  pages        = {{1245--1253}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{AIDS}},
  title        = {{Kynurenine/tryptophan ratio for detection of active tuberculosis in adults with HIV prior to antiretroviral therapy}},
  url          = {{http://dx.doi.org/10.1097/QAD.0000000000003235}},
  doi          = {{10.1097/QAD.0000000000003235}},
  volume       = {{36}},
  year         = {{2022}},
}